8JKQ

T95R mutant IRF4 DNA-binding domain bound to an DNA containing GACA motif

8JKQ の概要

• エントリーDOI: 10.2210/pdb8jkq/pdb
• 分子名称: GACA-Forward, GACA-Reverse, Interferon regulatory factor 4 (3 entities in total)
• 機能のキーワード: irf4, transcription factor, protein-dna complex, transcription
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 77887.08

構造登録者

Wang, G.,Feng, X.,Ding, J. (登録日: 2023-06-01, 公開日: 2023-09-20, 最終更新日: 2023-11-15)

主引用文献

Wang, G.,Feng, X.,Ding, J.
Molecular basis for the functional roles of the multimorphic T95R mutation of IRF4 causing human autosomal dominant combined immunodeficiency.
Structure, 31:1441-, 2023

PubMed Abstract: Interferon regulatory factor 4 (IRF4) is a transcription factor that regulates the development and function of immune cells. Recently, a new multimorphic mutation T95R was identified in the IRF4 DNA-binding domain (DBD) in patients with autosomal dominant combined immune deficiency. Here, we characterized the interactions of the wild-type IRF4-DBD (IRF4-DBD) and T95R mutant (IRF4-DBD) with a canonical DNA sequence and several noncanonical DNA sequences. We found that compared to IRF4-DBD, IRF4-DBD exhibits higher binding affinities for both canonical and noncanonical DNAs, with the highest preference for the noncanonical GATA sequence. The crystal structures of IRF4-DBD in complex with the GATA sequence and IRF4-DBD in complexes with both canonical and noncanonical DNAs were determined, showing that the T95R mutation enhances the interactions of IRF4-DBD with the canonical and noncanonical DNAs to achieve higher affinity and specificity. Collectively, our data provide the molecular basis for the gain-of-function and new function of IRF4.

PubMed: 37683642
DOI: 10.1016/j.str.2023.08.013

実験手法

X-RAY DIFFRACTION (3.09 Å)